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PLoS Genet. 2017 Oct 13;13(10):e1007051. doi: 10.1371/journal.pgen.1007051. eCollection 2017 Oct.

Condensin II and GAIT complexes cooperate to restrict LINE-1 retrotransposition in epithelial cells.

Author information

1
Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.
2
Department of Human Genetics, University of Michigan School of Medicine, Ann Arbor, MI, United States of America.
3
Proteomics Core, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.
4
Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, United States of America.

Abstract

LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1). GAIT has been shown to inhibit translation of mRNAs encoding inflammatory proteins in myeloid cells by preventing the binding of the translation initiation complex, in response to Interferon gamma (IFN-γ). Excitingly, our data show that Condensin II promotes complexation of GAIT subunits. Furthermore, RNA-Immunoprecipitation experiments in epithelial cells demonstrate that Condensin II and GAIT subunits associate with L1 RNA in a co-dependent manner, independent of IFN-γ. These findings suggest that cooperation between the Condensin II and GAIT complexes may facilitate a novel mechanism of L1 repression, thus contributing to the maintenance of genome stability in somatic cells.

PMID:
29028794
PMCID:
PMC5656329
DOI:
10.1371/journal.pgen.1007051
[Indexed for MEDLINE]
Free PMC Article

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